Nintedanib zentiva

Package leaflet: Information for the patient

Nintedanib Zentiva, 100 mg, soft capsules
Nintedanibum
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Nintedanib Zentiva is and what it is used for
2. What you need to know before taking Nintedanib Zentiva
3. How to take Nintedanib Zentiva
4. Possible side effects
5. How to store Nintedanib Zentiva
6. Contents of the pack and other information

1. What Nintedanib Zentiva is and what it is used for

Nintedanib Zentiva contains the active substance nintedanib, which belongs to a group of medicines called tyrosine kinase inhibitors. It is used to treat the following conditions:

Idiopathic pulmonary fibrosis (IPF) in adults
IPF is a disease in which lung tissue gradually becomes thicker, stiffer, and scarred. This scarring reduces the ability of the lungs to transfer oxygen into the blood. Deep breathing becomes difficult. This medicine helps slow down further scarring and stiffening of the lungs.

Other chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype in adults
Besides IPF, there are other conditions in which lung tissue over time becomes thicker, stiffer, and scarred (lung fibrosis), and which continuously worsen (progressive phenotype).
Examples of these conditions include hypersensitivity pneumonitis, autoimmune ILD (e.g. ILD associated with rheumatoid arthritis), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. This medicine helps slow down further scarring and stiffening of the lungs.

Clinically significant, progressive fibrosing interstitial lung diseases (ILD) in children and adolescents aged 6 to 17 years
In patients with childhood interstitial lung disease (chILD), lung fibrosis may occur. In such cases, the tissue in the lungs of children and adolescents gradually becomes thickened, stiff, and scarred over time. Nintedanib Zentiva helps slow down further scarring and stiffening of the lungs.

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, adolescents, and children aged 6 years and older
Systemic sclerosis (SSc), also known as scleroderma (and juvenile systemic sclerosis in children and adolescents), is a rare autoimmune disease affecting connective tissue in many parts of the body. Systemic sclerosis (SSc) causes fibrosis (scarring and stiffening) of the skin and other internal organs, such as the lungs. The presence of fibrosis in the lungs is called interstitial lung disease (ILD), and the condition is therefore known as SSc-ILD. Lung fibrosis reduces the ability to deliver oxygen into the bloodstream, making breathing difficult.
This medicine helps slow down further scarring and stiffening of the lungs.

2. Important information before taking Nintedanib Zentiva

When not to take Nintedanib Zentiva

• if the patient is allergic to nintedanib or any of the other ingredients of this medicine (listed in section 6),
• if the patient is pregnant.

Warnings and precautions
Before starting treatment with Nintedanib Zentiva, discuss with your doctor or
pharmacist if:

• the patient has or has had liver problems,
• the patient has or has had kidney problems or protein in the urine has been detected,
• the patient has or has had bleeding problems,
• the patient is taking medicines that reduce blood clotting (such as warfarin, phenprocoumon, heparin) to prevent blood clots,
• the patient is taking pirfenidone, as this may increase the risk of diarrhoea, nausea, vomiting and liver problems,
• the patient has or has had heart problems (e.g. heart attack),
• the patient has recently undergone surgery. Nintedanib may affect wound healing. Therefore, treatment with this medicine is usually paused for a certain period if the patient undergoes surgery. Your doctor will decide when treatment should be resumed.
• if the patient has high blood pressure,
• if the patient has pulmonary hypertension (high blood pressure in the blood vessels of the lungs),
• if the patient has or has previously had an aneurysm (a weakened and enlarged blood vessel) or a tear in the blood vessel wall.

Based on this information, the doctor may perform blood tests, for example,
to check liver function. The doctor will discuss the results of these tests with the patient and
decide whether the patient can take Nintedanib Zentiva.
Contact your doctor immediately if, while taking this medicine:

• the patient develops diarrhoea. Early treatment of diarrhoea is important (see section 4);

• the patient experiences vomiting or nausea (feeling sick);

• the patient develops unexplained symptoms such as yellowing of the skin or whites of the eyes (jaundice), dark or brown (tea-coloured) urine, pain in the upper right part of the abdomen, more frequent bleeding or bruising than usual, or a feeling of fatigue. These may be symptoms of serious liver problems;

• the patient experiences severe stomach pain, fever, chills, nausea, vomiting, or a hard abdomen or bloating, as these may be symptoms of a hole in the intestinal wall (gastrointestinal perforation). The patient should also inform the doctor if they have previously had peptic ulcers or diverticular disease of the intestine, or
  if the patient is taking anti-inflammatory medicines (non-steroidal anti-inflammatory drugs, NSAIDs) (used to treat pain and swelling) or steroids (used
  to treat inflammatory and allergic conditions) at the same time, as these factors increase this risk;

• the patient simultaneously experiences severe pain or cramps in the abdomen, red blood in the stool or diarrhoea, as these may be symptoms of intestinal inflammation due to inadequate blood supply;

• the patient develops pain, swelling, redness and increased temperature in a limb, as these may be symptoms of a blood clot in a vein (a type of blood vessel);

• the patient experiences chest tightness or pain, typically on the left side of the body, pain in the neck, jaw, arm or hand, rapid heartbeat, shortness of breath, nausea, vomiting, as these may be symptoms of a heart attack;

• the patient experiences serious bleeding;

• the patient develops bruising, bleeding, fever, fatigue and confusion. This may be a sign of blood vessel damage called thrombotic microangiopathy (TMA),

• the patient develops symptoms such as headache, visual disturbances, disorientation, seizures or other neurological disturbances such as weakness in the arms or legs, with or without high blood pressure. These may be symptoms of a brain disorder called posterior reversible encephalopathy syndrome (PRES).

Children and adolescents
Nintedanib Zentiva must not be given to children under 6 years of age.
The doctor may perform regular dental examinations at least every 6 months until tooth development is complete and monitor the patient’s growth once a year (bone imaging) during treatment with this medicine.
Nintedanib Zentiva and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including herbal products and over-the-counter medicines.
Nintedanib Zentiva may interact with certain other medicines. The following medicines
may increase the blood concentration of nintedanib and thereby increase the risk of
adverse effects (see section 4):

• a medicine used to treat fungal infections (ketoconazole),
• a medicine used to treat bacterial infections (erythromycin),
• a medicine affecting the immune system (cyclosporine).

The following medicines are examples of those that may reduce the blood concentration of nintedanib and thereby reduce the effectiveness of Nintedanib Zentiva:

• an antibiotic used to treat tuberculosis (rifampicin),
• medicines used to treat epileptic seizures (carbamazepine, phenytoin),
• a herbal medicine used to treat depression (St. John’s wort).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before taking this medicine.
Pregnancy
Do not take this medicine during pregnancy, as it may harm the unborn child and cause birth defects.
A pregnancy test must be performed before starting treatment to ensure the patient is not pregnant. The patient should discuss this with her treating doctor.
Contraceptive medicines

• Women who could become pregnant must use a highly effective method of contraception to prevent pregnancy, both when starting treatment with Nintedanib Zentiva, throughout the entire treatment period, and for at least 3 months after stopping treatment.
• The best contraceptive methods should be discussed with the treating doctor.
• Vomiting and/or diarrhoea or other gastrointestinal disturbances may affect the absorption of oral hormonal contraceptives, such as contraceptive pills, and may reduce their effectiveness. Therefore, if such disturbances occur, discuss with your doctor the use of an alternative, more appropriate method of contraception.
• If the patient becomes pregnant or suspects she may be pregnant while being treated with this medicine, she should immediately inform her doctor or pharmacist.

Breastfeeding
Do not breastfeed while taking this medicine, as there is a risk of adverse effects in the breastfed child.
Driving and using machines
This medicine may have a minor influence on the ability to drive and use machines. If the patient feels nauseous, they should not drive or operate machinery.

3. How to take Nintedanib Zentiva

This medicine should always be taken exactly as instructed by your doctor or pharmacist.
If in doubt, consult your doctor or pharmacist.
Take the capsules twice daily, approximately 12 hours apart, at approximately the same
time each day, for example one capsule in the morning and one in the evening. This will
ensure a constant level of nintedanib in the patient's bloodstream. Swallow the capsules
whole with water; do not suck or chew the capsules. It is recommended to take the
capsules with food, i.e. during, immediately before, or immediately after a meal. The
capsules must not be opened or crushed (see section 5).
To make swallowing easier, the capsules may be taken with a small amount (one teaspoon)
of cold or soft food at room temperature, such as apple sauce or chocolate pudding. The
capsules should be swallowed immediately and not chewed, so that the capsule remains
intact.

Adults
The recommended dose is one 100 mg capsule taken twice daily (total 200 mg per day).
Do not take more than the recommended two soft capsules of Nintedanib Zentiva 100 mg per
day.
If the patient does not tolerate the recommended dose of two Nintedanib Zentiva 100 mg
capsules per day (see possible side effects in section 4), the doctor may advise discontinuing
treatment with this medicine. Do not reduce the dose or stop treatment on your own without
first consulting your doctor.

Use in children and adolescents
The recommended dose depends on the patient's body weight.
Inform the doctor if, at any time during treatment, the patient's body weight drops below
13.5 kg.
Inform the doctor if the patient has liver problems.
The doctor will determine the correct dose. The doctor may adjust the dose as treatment
progresses.
If the patient does not tolerate the recommended daily dose of Nintedanib Zentiva capsules
(see possible side effects in section 4), the doctor may reduce the daily dose of Nintedanib
Zentiva.
Do not reduce the dose or stop treatment on your own without first discussing it with your
doctor.

Dosing of Nintedanib Zentiva capsules in children and adolescents according to body weight:

Nintedanib Zentiva is available only in soft capsules with a dose of 100 mg and 150 mg. Therefore, it is not possible to administer Nintedanib Zentiva to pediatric patients who require a dose lower than the full 100 mg dose. If an alternative dose is required, other nintedanib-containing products that offer such options should be used.
Taking more Nintedanib Zentiva than recommended
Contact your doctor or pharmacist immediately.
Missing a dose of Nintedanib Zentiva
Do not take two capsules together if you have missed a previous dose. Take the next dose of Nintedanib Zentiva according to your usual schedule as prescribed by your doctor or pharmacist.
Stopping treatment with Nintedanib Zentiva
Do not stop taking Nintedanib Zentiva without first consulting your doctor. It is important to take the medicine regularly and daily for as long as your doctor recommends.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Particular attention should be paid to the following adverse reactions
during treatment with Nintedanib Zentiva.
Diarrhoea (Very common, may occur in more than 1 in 10 people)
Diarrhoea may lead to dehydration: loss of water and important substances (electrolytes,
such as sodium or potassium) from the body. If the first symptoms of diarrhoea occur,
drink plenty of fluids and contact your doctor immediately. Start appropriate anti-diarrhoeal treatment as soon as possible, for example with loperamide.
The following other adverse reactions have been observed with the use of this medicine.
If any adverse reactions occur in the patient, inform the doctor.
Idiopathic pulmonary fibrosis (IPF)
Very common adverse reactions (may occur in more than 1 in 10 people)

• nausea,
• abdominal pain,
• abnormal liver function test results.

Common adverse reactions (may occur in less than 1 in 10 people)

• vomiting,
• loss of appetite,
• weight decrease,
• bleeding,
• rash,
• headache.

Uncommon adverse reactions (may occur in less than 1 in 100 people)

• pancreatitis,
• colitis,
• serious liver problems,
• low platelet count (thrombocytopenia),
• high blood pressure (hypertension),
• jaundice, i.e. yellowing of the skin and whites of the eyes due to high bilirubin levels,
• itching,
• myocardial infarction,
• excessive hair loss (alopecia),
• increased protein concentration in urine (proteinuria).

Frequency not known (frequency cannot be estimated from the available data)

• renal failure,
• enlargement and weakening of the blood vessel wall or rupture of the blood vessel wall (aneurysm and arterial dissection),
• brain disorder with symptoms such as headache, visual disturbances, confusion, seizures or other neurological disorders such as weakness in arms or legs, with or without high blood pressure (posterior reversible encephalopathy syndrome).

Other chronic fibrosing interstitial lung diseases (ILD) with progressive phenotype
Very common adverse reactions (may occur in more than 1 in 10 people)

• nausea,
• vomiting,
• loss of appetite,
• abdominal pain,
• abnormal liver function test results.

Common adverse reactions (may occur in less than 1 in 10 people)

• weight decrease,
• high blood pressure (hypertension),
• bleeding,
• serious liver problems,
• rash,
• headache.

Uncommon adverse reactions (may occur in less than 1 in 100 people)

• pancreatitis,
• colitis,
• low platelet count (thrombocytopenia),
• jaundice, i.e. yellowing of the skin and whites of the eyes due to high bilirubin levels,
• itching,
• myocardial infarction,
• excessive hair loss (alopecia),
• increased protein concentration in urine (proteinuria).

Frequency not known (frequency cannot be estimated from the available data)

• renal failure,
• enlargement and weakening of the blood vessel wall or rupture of the blood vessel wall (aneurysm and arterial dissection),
• brain disorder with symptoms such as headache, visual disturbances, confusion, seizures or other neurological disorders such as weakness in arms or legs, with or without high blood pressure (posterior reversible encephalopathy syndrome).

Systemic sclerosis-associated interstitial lung disease (SSc-ILD)
Very common adverse reactions (may occur in more than 1 in 10 people)

• nausea,
• vomiting,
• abdominal pain,
• abnormal liver function test results.

Common adverse reactions (may occur in less than 1 in 10 people)

• bleeding,
• high blood pressure (hypertension),
• loss of appetite,
• weight decrease,
• headache.

Uncommon adverse reactions (may occur in less than 1 in 100 people)

• colitis,
• serious liver problems,
• renal failure,
• low platelet count (thrombocytopenia),
• rash,
• itching.

Frequency not known (frequency cannot be estimated from the available data)

• myocardial infarction,
• pancreatitis,
• jaundice, i.e. yellowing of the skin and whites of the eyes due to high bilirubin levels,
• enlargement and weakening of the blood vessel wall or rupture of the blood vessel wall (aneurysm and arterial dissection),
• excessive hair loss (alopecia),
• increased protein concentration in urine (proteinuria),
• brain disorder with symptoms such as headache, visual disturbances, confusion, seizures or other neurological disorders such as weakness in arms or legs, with or without high blood pressure (posterior reversible encephalopathy syndrome).

Fibrosing interstitial lung diseases (ILD) in children and adolescents
Adverse reactions in children and adolescents were similar to those observed in adult
patients. Consult a doctor if any adverse reactions occur in the patient.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C,
02-222 Warsaw, phone: 22 49-21-301, fax: 22 49-21-309,
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder or its representative.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Nintedanib Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the stated month.
This medicine does not require any special storage conditions.
Do not use this medicine if the blister containing the capsules is open or if a capsule appears damaged.
In case of contact with the capsule contents, wash hands immediately with plenty of water (see section 3).
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Package contents and other information

What Nintedanib Zentiva contains

• The active substance is nintedanib. Each capsule contains 100 mg of nintedanib (as nintedanib esilate).
• The other ingredients are:
  Capsule contents: medium-chain triglycerides, solid fat, polyglyceryl-3 dioleate
  Capsule shell: gelatin, glycerol, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172), purified water
  Printing ink: shellac, carmine (E 120), propylene glycol (E 1520), simethicone

What Nintedanib Zentiva looks like and contents of the pack

Nintedanib Zentiva 100 mg is an opaque, peach-coloured, elongated soft capsule containing a yellow, viscous suspension, printed in red with "NT 100", and 16 mm in length.

Nintedanib Zentiva 100 mg soft capsules are available in unit-dose perforated blisters made of OPA/Aluminium/PVC/Aluminium, packed in a cardboard carton.

Pack sizes:
30 x 1 soft capsule
60 x 1 soft capsule
120 x 1 soft capsule

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer/Importer
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola PLA 3000
Malta
Adalvo Limited
Malta Life Sciences Park Building 1 Level 4
Sir Temi Zammit Buildings
San Gwann Industrial Estate
SGN 3000 San Gwann
Malta
QUALIMETRIX S.A.
579 MESOGEION AVENUE AGIA PARASKEVI,
15343 Athens
Greece

This medicinal product has been authorised in the Member States of the European Economic Area under the following names:
Germany: Nintedanib Zentiva 100 mg Weichkapseln
Spain: NINTEDANIB ZENTIVA 100 MG CAPSULAS BLANDAS EFG
France: NINTEDANIB ZENTIVA 100 mg, capsule molle
Lithuania: Nintedanib Zentiva 100 mg minkštosios Kapsulės
Latvia: Nintedanib Zentiva 100 mg mīkstās kapsulas
Denmark, Estonia, Finland, Iceland, Poland, Norway, Portugal, Sweden: Nintedanib Zentiva

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00